The transmembrane human protein thrombomodulin (TM), as a critical regulator of the protein C pathway, represents the major anticoagulant mechanism that is operative in both normal and injured blood vessels under physiologic conditions in vivo. An effective blood-contacting surface is dependent upon the presence of physiologically relevant antithrombogenic mechanisms that are incorporated into an engineered blood-material interface. Full length native human TM can be incorporated into membrane-mimetic films or surfaces by fusion/adsorption processes; a major drawback of these materials, however, is a loss of TM stability and/or functional activity with time. Moreover, in existing protocols for covalent immobilization of TM onto polymeric surfaces, the protein immobilization procedure involves freely available amino or carboxyl functionalities of TM, some of which may be within or near a bioactive site. The use of such functionalities can significantly reduce the functional bioactivity of TM after surface coupling. There is therefore a need for compositions and methods in this field to serve as effective alternatives.